All optic neuropathies primarily affect the inner layers of the retina. In particular, the nerve fiber layer (NFL), the ganglion cell layer (GCL) and the inner plexiform layer (IPL) are most affected. In contrast, the inner nuclear layer (INL) is less affected and the outer layers are not affected [1]. Because each of the 3 inner layers of the retina contain different parts of the retinal ganglion cells (NFL contains the axons, GCL contains the cell bodies, and IPL contains the dendrites), diagnostic methods that take this local anatomical variation into account will generally have better diagnostic specificity. For instance, although measurements of the overall retinal thickness will provide general diagnostic information, measurements that focus around the area nearby the optic nerve head (ONH, also called optic disc) will provide much more diagnostic information because the NFL is thickest in this area. In the macula (area around the fovea), all 3 inner layers contributes diagnostic information, therefore, it is best to measure the combined Inner Retinal Layers that include the NFL, GCL and IPL.
While this principle is simple in theory, it is not easy in practice. Take the diagnosis of glaucoma for example. Glaucomatous optic neuropathy is a result of several progressive alterations in ocular anatomy: loss of retinal ganglion cells (RGCs), thinning of the retinal nerve fiber layer (NFL), and cupping of the optic disc. Thus, it stands to reason that these anatomical changes can be used as diagnostic indicators for glaucoma. Unfortunately, in practice, this knowledge cannot be easily utilized in diagnostic methods. RGC loss cannot be seen on conventional slit-lamp ophthalmic examinations. Likewise, NFL bundle defects are difficult to detect on clinical examination. Although red-free fundus photography is capable of detecting changes in the vascular system and nerve fibers of the retina, the technique is rarely used in clinical practice. Thus, clinical diagnosis of glaucoma is currently based only on characteristic optic nerve cupping in conjunction with tests for the corresponding visual field deficits in the patient.
However, since a significant loss to RGC population can occur prior to detectable visual field deficits, and this structural loss can precede detectable function loss by up to 5 years, current methods for clinical diagnosis of glaucoma are not adequate for early detection of the disease. Thus, there currently exists an unmet need for detection and prognostication methods that are capable of identifying and quantifying changes in the RGC population which are also easy to administer in clinical settings.